Although the exact mechanisms leading to acne are not known, antiandrogens, retinoic acid, steroids and antibiotics, inter alia have generally been proposed for its treatment, as described in U.S. Pat. Nos. 4,139,638; 4,161,540; 4,191,775; 4,344,943; and West German OLS no. 2,840,144.
PFB relates to the removal of hair by shaving or plucking. It has been treated by procedures such as the use of electric clippers or depilatories for hair removal, or by topical treatment with tretinoin (Retin-A), benzoyl peroxide, chlorohydroxyquinoline, chloroalkylphenols, phospholipids in combination with wheat germ oil and vitamin E, alpha-hydroxy acids, salicylic acid in combination with glucocorticoids and sulfur as shown for example in U.S. Pat. Nos. 4,228,163, 4,463,016; 4,525,344; 4,775,530; and 4,944,939; and in Klingman et al., Arch. Dermatol., vol. 107, 551-52 (1973).
Many of the treatments for PFB, and particularly for acne, produce such serious side effects that the treatment can be justified only in the most severe cases; other treatments are of limited effectiveness.
The compound 2-(difluoromethyl) ornithine (DFMO, 2-difluoromethyl-2.5-diaminopentanoic acid) and other inhibitors of ornithine dicarboxylase have been proposed for use in treating cancer and certain non-malignant diseases such as erythroderma, psoriasis, and some forms of dermatitis, etc. as described in Splinter et al., Eur. J. Cancer and Clin. Oncology, Vol. 22:I-E, 61-67 (1985); McCullough et al. J. Investig. Dermatology, Vol. 85, 518-521 (1985); McCullough et al., J. Investig. Dermatology, Vol. 81, 388-392 (1983); Kousa et al., Acta Dermatovener (Stockholm) Vol. 62, 221-224 (1982); and U.S. Pat. No. 4,207,315.
It has now been found that topical administration of a cytostatic nontoxic agent such as 2(difluoromethyl)-2.5-diaminopentanoic acid (d-difluoromethylornithine, DFMO) which inhibits the activity of the enzyme ornithine decarboxylase can be used to effectively ameliorate or control acne and/or PFB in patients with minimal or no unwanted side effects. DFMO can be used in combination with a topically active sebosuppressive agent such as an antiandrogen or a retinoid to gain the benefits of such agents for the treatment. Among the preferred inhibitors of ornithine decarboxylase, in addition to DFMO, which can be used in the present invention, are alpha-ethynyl ornithine; 6-heptyne-2,5-diamine; and esters of (E)-2-fluoromethyldehydroornithine. In choosing ODC inhibitors for use in the practice of the present invention it is important to avoid those having undesirable secondary pharmacological effects such as 5-hexyne-l,4-diamine. The inhibitors of ornithine decarboxylase are employed by dissolving or dispersing them in a conventional non-toxic pharmacologically acceptable vehicle or carrier which may be in the form of a lotion, cream, salve, ointment, or stick composition; while the precise concentration of inhibitor in vehicle or carrier is not critical it is generally desired that the composition contain from 1 to 20% of inhibitor by weight so that it can be applied to the affected areas of the skin of patients suffering from acne or PFB, particularly to the pimples or inflamed areas of the skin, at the rate of 40 to 800 micrograms per square centimeter. The composition is preferably applied only to the pustules, vacuoles or inflamed areas of the skin although application to adjacent areas need not be avoided.
Among the antiandrogens which can be used along with the ODC inhibitor are cyproterone acetate, chlormadinone acetate, 17-alpha-propyltestosterone, 17-alpha-allyitestosterone, .alpha.-.alpha.-.alpha.-trifluoro-2-methyl-4'-nitro-m-propionotoluidide, 6.alpha.-bromo-17.beta.-hydroxy-17.alpha.-methyl-4-oxa-5.alpha.-androstane -3-one, 17.beta.-acetoxy-4.alpha.,5cyclo-A-homo-B-nor-5.alpha.-androst-1-ene-3-one , and spironolactone. For minimal alterations of other androgen-mediated bodily functions through systemic action, 17-alpha-propyltestosterone or 17-alpha-allyltestosterone are preferred.
The following examples will serve to illustrate further the nature of the invention without acting as a limitation upon its scope.